Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission
We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/5/1458 |
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| author | Beryl L. Manning-Geist Sacha Gnjatic Carol Aghajanian Jason Konner Sarah H. Kim Debra Sarasohn Krysten Soldan William P. Tew Nicholas J. Sarlis Dmitriy Zamarin Sara Kravetz Ilaria Laface Teresa Rasalan-Ho Jingjing Qi Phillip Wong Paul J. Sabbatini Roisin E. O’Cearbhaill |
| author_facet | Beryl L. Manning-Geist Sacha Gnjatic Carol Aghajanian Jason Konner Sarah H. Kim Debra Sarasohn Krysten Soldan William P. Tew Nicholas J. Sarlis Dmitriy Zamarin Sara Kravetz Ilaria Laface Teresa Rasalan-Ho Jingjing Qi Phillip Wong Paul J. Sabbatini Roisin E. O’Cearbhaill |
| author_sort | Beryl L. Manning-Geist |
| collection | DOAJ |
| description | We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade ≥3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate. |
| first_indexed | 2024-03-11T07:29:31Z |
| format | Article |
| id | doaj.art-2fae61eec6c7477bab9bf0842ed06642 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T07:29:31Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2fae61eec6c7477bab9bf0842ed066422023-11-17T07:24:24ZengMDPI AGCancers2072-66942023-02-01155145810.3390/cancers15051458Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third RemissionBeryl L. Manning-Geist0Sacha Gnjatic1Carol Aghajanian2Jason Konner3Sarah H. Kim4Debra Sarasohn5Krysten Soldan6William P. Tew7Nicholas J. Sarlis8Dmitriy Zamarin9Sara Kravetz10Ilaria Laface11Teresa Rasalan-Ho12Jingjing Qi13Phillip Wong14Paul J. Sabbatini15Roisin E. O’Cearbhaill16Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USAGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAGynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USASELLAS Life Sciences Group, Inc., New York, NY 10036, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USAGynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USATisch Cancer Institute, Precision Immunology Institute, Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USAImmune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAImmune Monitoring Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USADepartment of Medicine, Weill Cornell Medical Center, New York, NY 10065, USAWe examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms’ Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti–PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity. One-year progression-free survival (PFS) was correlated to T-cell responses and WT1-specific immunoglobulin (Ig)G levels. Eleven patients were enrolled; seven experienced a grade 1 adverse event, and one experienced a grade ≥3 adverse event considered a dose-limiting toxicity. Ten (91%) of eleven patients had T-cell responses to WT1 peptides. Seven (88%) of eight evaluable patients had IgG against WT1 antigen and full-length protein. In evaluable patients who received >2 treatments of galinpepimut-S and nivolumab, the 1-year PFS rate was 70%. Coadministration of galinpepimut-S and nivolumab demonstrated a tolerable toxicity profile and induced immune responses, as indicated by immunophenotyping and WT1-specific IgG production. Exploratory analysis for efficacy yielded a promising 1-year PFS rate.https://www.mdpi.com/2072-6694/15/5/1458immunotherapyantigensvaccineimmunogenicityprogrammed cell death 1 receptorepithelial ovarian cancer |
| spellingShingle | Beryl L. Manning-Geist Sacha Gnjatic Carol Aghajanian Jason Konner Sarah H. Kim Debra Sarasohn Krysten Soldan William P. Tew Nicholas J. Sarlis Dmitriy Zamarin Sara Kravetz Ilaria Laface Teresa Rasalan-Ho Jingjing Qi Phillip Wong Paul J. Sabbatini Roisin E. O’Cearbhaill Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission Cancers immunotherapy antigens vaccine immunogenicity programmed cell death 1 receptor epithelial ovarian cancer |
| title | Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission |
| title_full | Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission |
| title_fullStr | Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission |
| title_full_unstemmed | Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission |
| title_short | Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission |
| title_sort | phase i study of a multivalent wt1 peptide vaccine galinpepimut s in combination with nivolumab in patients with wt1 expressing ovarian cancer in second or third remission |
| topic | immunotherapy antigens vaccine immunogenicity programmed cell death 1 receptor epithelial ovarian cancer |
| url | https://www.mdpi.com/2072-6694/15/5/1458 |
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